Evolution of Fluconazole-Resistant <named-content content-type="genus-species">Candida albicans</named-content> Strains by Drug-Induced Mating Competence and Parasexual Recombination
ABSTRACT The clonal population structure of Candida albicans suggests that (para)sexual recombination does not play an important role in the lifestyle of this opportunistic fungal pathogen, an assumption that is strengthened by the fact that most C. albicans strains are heterozygous at the mating ty...
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American Society for Microbiology
2019
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oai:doaj.org-article:9ac3fa45865f4cf384a318860cc528e92021-11-15T15:55:13ZEvolution of Fluconazole-Resistant <named-content content-type="genus-species">Candida albicans</named-content> Strains by Drug-Induced Mating Competence and Parasexual Recombination10.1128/mBio.02740-182150-7511https://doaj.org/article/9ac3fa45865f4cf384a318860cc528e92019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02740-18https://doaj.org/toc/2150-7511ABSTRACT The clonal population structure of Candida albicans suggests that (para)sexual recombination does not play an important role in the lifestyle of this opportunistic fungal pathogen, an assumption that is strengthened by the fact that most C. albicans strains are heterozygous at the mating type locus (MTL) and therefore mating-incompetent. On the other hand, mating might occur within clonal populations and allow the combination of advantageous traits that were acquired by individual cells to adapt to adverse conditions. We have investigated if parasexual recombination may be involved in the evolution of highly drug-resistant strains exhibiting multiple resistance mechanisms against fluconazole, an antifungal drug that is commonly used to treat infections by C. albicans. Growth of strains that were heterozygous for MTL and different fluconazole resistance mutations in the presence of the drug resulted in the emergence of derivatives that had become homozygous for the mutated allele and the mating type locus and exhibited increased drug resistance. When MTLa/a and MTLα/α cells of these strains were mixed in all possible combinations, we could isolate mating products containing the genetic material from both parents. The initial mating products did not exhibit higher drug resistance than their parental strains, but further propagation under selective pressure resulted in the loss of the wild-type alleles and increased fluconazole resistance. Therefore, fluconazole treatment not only selects for resistance mutations but also promotes genomic alterations that confer mating competence, which allows cells in an originally clonal population to exchange individually acquired resistance mechanisms and generate highly drug-resistant progeny. IMPORTANCE Sexual reproduction is an important mechanism in the evolution of species, since it allows the combination of advantageous traits of individual members in a population. The pathogenic yeast Candida albicans is a diploid organism that normally propagates in a clonal fashion, because heterozygosity at the mating type locus (MTL) inhibits mating between cells. Here we show that C. albicans cells that have acquired drug resistance mutations during treatment with the commonly used antifungal agent fluconazole rapidly develop further increased resistance by genome rearrangements that result in simultaneous loss of heterozygosity for the mutated allele and the mating type locus. This enables the drug-resistant cells of a population to switch to the mating-competent opaque morphology and mate with each other to combine different individually acquired resistance mechanisms. The tetraploid mating products reassort their merged genomes and, under selective pressure by the drug, generate highly resistant progeny that have retained the advantageous mutated alleles. Parasexual propagation, promoted by stress-induced genome rearrangements that result in the acquisition of mating competence in cells with adaptive mutations, may therefore be an important mechanism in the evolution of C. albicans populations.Christina PoppBernardo Ramírez-ZavalaSonja SchwanfelderInes KrügerJoachim MorschhäuserAmerican Society for MicrobiologyarticleCandida albicansdrug resistance evolutionmatingparasexual recombinationMicrobiologyQR1-502ENmBio, Vol 10, Iss 1 (2019) |
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DOAJ |
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DOAJ |
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EN |
| topic |
Candida albicans drug resistance evolution mating parasexual recombination Microbiology QR1-502 |
| spellingShingle |
Candida albicans drug resistance evolution mating parasexual recombination Microbiology QR1-502 Christina Popp Bernardo Ramírez-Zavala Sonja Schwanfelder Ines Krüger Joachim Morschhäuser Evolution of Fluconazole-Resistant <named-content content-type="genus-species">Candida albicans</named-content> Strains by Drug-Induced Mating Competence and Parasexual Recombination |
| description |
ABSTRACT The clonal population structure of Candida albicans suggests that (para)sexual recombination does not play an important role in the lifestyle of this opportunistic fungal pathogen, an assumption that is strengthened by the fact that most C. albicans strains are heterozygous at the mating type locus (MTL) and therefore mating-incompetent. On the other hand, mating might occur within clonal populations and allow the combination of advantageous traits that were acquired by individual cells to adapt to adverse conditions. We have investigated if parasexual recombination may be involved in the evolution of highly drug-resistant strains exhibiting multiple resistance mechanisms against fluconazole, an antifungal drug that is commonly used to treat infections by C. albicans. Growth of strains that were heterozygous for MTL and different fluconazole resistance mutations in the presence of the drug resulted in the emergence of derivatives that had become homozygous for the mutated allele and the mating type locus and exhibited increased drug resistance. When MTLa/a and MTLα/α cells of these strains were mixed in all possible combinations, we could isolate mating products containing the genetic material from both parents. The initial mating products did not exhibit higher drug resistance than their parental strains, but further propagation under selective pressure resulted in the loss of the wild-type alleles and increased fluconazole resistance. Therefore, fluconazole treatment not only selects for resistance mutations but also promotes genomic alterations that confer mating competence, which allows cells in an originally clonal population to exchange individually acquired resistance mechanisms and generate highly drug-resistant progeny. IMPORTANCE Sexual reproduction is an important mechanism in the evolution of species, since it allows the combination of advantageous traits of individual members in a population. The pathogenic yeast Candida albicans is a diploid organism that normally propagates in a clonal fashion, because heterozygosity at the mating type locus (MTL) inhibits mating between cells. Here we show that C. albicans cells that have acquired drug resistance mutations during treatment with the commonly used antifungal agent fluconazole rapidly develop further increased resistance by genome rearrangements that result in simultaneous loss of heterozygosity for the mutated allele and the mating type locus. This enables the drug-resistant cells of a population to switch to the mating-competent opaque morphology and mate with each other to combine different individually acquired resistance mechanisms. The tetraploid mating products reassort their merged genomes and, under selective pressure by the drug, generate highly resistant progeny that have retained the advantageous mutated alleles. Parasexual propagation, promoted by stress-induced genome rearrangements that result in the acquisition of mating competence in cells with adaptive mutations, may therefore be an important mechanism in the evolution of C. albicans populations. |
| format |
article |
| author |
Christina Popp Bernardo Ramírez-Zavala Sonja Schwanfelder Ines Krüger Joachim Morschhäuser |
| author_facet |
Christina Popp Bernardo Ramírez-Zavala Sonja Schwanfelder Ines Krüger Joachim Morschhäuser |
| author_sort |
Christina Popp |
| title |
Evolution of Fluconazole-Resistant <named-content content-type="genus-species">Candida albicans</named-content> Strains by Drug-Induced Mating Competence and Parasexual Recombination |
| title_short |
Evolution of Fluconazole-Resistant <named-content content-type="genus-species">Candida albicans</named-content> Strains by Drug-Induced Mating Competence and Parasexual Recombination |
| title_full |
Evolution of Fluconazole-Resistant <named-content content-type="genus-species">Candida albicans</named-content> Strains by Drug-Induced Mating Competence and Parasexual Recombination |
| title_fullStr |
Evolution of Fluconazole-Resistant <named-content content-type="genus-species">Candida albicans</named-content> Strains by Drug-Induced Mating Competence and Parasexual Recombination |
| title_full_unstemmed |
Evolution of Fluconazole-Resistant <named-content content-type="genus-species">Candida albicans</named-content> Strains by Drug-Induced Mating Competence and Parasexual Recombination |
| title_sort |
evolution of fluconazole-resistant <named-content content-type="genus-species">candida albicans</named-content> strains by drug-induced mating competence and parasexual recombination |
| publisher |
American Society for Microbiology |
| publishDate |
2019 |
| url |
https://doaj.org/article/9ac3fa45865f4cf384a318860cc528e9 |
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